An analysis of available evidence challenges the
NCEP's recommendation for titration to very low levels.
The National Cholesterol Education Program recommends
titrating lipid-lowering therapy to reduce LDL cholesterol to very
low levels. For example, the goal is less than 70 mg/dL in people
at very high risk for cardiovascular events. Because the strength of
the evidence supporting the recommendation has been questioned, researchers
examined studies cited in major guidelines and searched the
literature for evidence of the independent association between these
cholesterol reductions and reductions in cardiovascular events.
Most clinical trials used fixed doses of statins. One
study randomized patients in two strata defined by their initial
response to simvastatin (40 mg/day). Simvastatin was associated with
no fewer cardiovascular events in patients who had larger decreases in
LDL levels than in patients with smaller decreases. The researchers also
examined cohort studies, all of which were analyses of data from
clinical trial participants. In these studies, greater LDL reductions
were associated with fewer cardiovascular events. However, these
observational analyses did not control for potential confounders,
including exposure to statins. No studies examined the association
between LDL level and cardiovascular events as a continuous outcome.
Comment: Clearly, most patients with (or at high risk for)
cardiovascular disease should be taking a statin. But titration to
very low targets can be difficult and costly, and it is not without
risk. So these researchers have made an important, relevant
observation: No solid evidence appears to support titration to very
low targets.
— Richard Saitz, MD, MPH, FACP, FASAM
Published in Journal Watch November 9, 2006
Citation(s):
Hayward RA et al. Narrative review: Lack of evidence for recommended low-density lipoprotein treatment targets: A solvable problem. Ann Intern Med 2006 Oct 3; 145:520-30.